竹叶椒化学成分的研究

自芸香科花椒属植物竹叶椒Zanthoxylum planispinum Sieb. et Zucc根的石油醚提取物中分离得到三种结晶。经物理常数测定,光谱(IR.NMR和MS)及X-射线单晶衍射分析,确定了化合物Ⅲ的绝对构型为(1R,2R,5R,6S)-2-(3′,4′-二甲氧基苯基)-6-(3″,4″-亚甲二氧苯基)双骈四氢呋喃,是一个新化合物,命名为竹叶椒脂素(L-planinin)。化合物Ⅰ为β-香木脂醇(β-amyrin),化合物Ⅱ为L-细辛脂素(L-asarinin),这三种化合物均系首次从本植物中分离得到。     

Hepatitis C infection among drug users attending general practice

Background The prevalence of hepatitis C (HCV) infection among injection drug users is high and addiction-related care is increasingly being provided by GPs in Ireland. Aims To determine the prevalence and associated factors of HCV infection among injecting drug users attending general practice. Methods The records of 571 patients attending 42 general practices in the Eastern Regional Health Authority (ERHA) area for methadone maintenance treatment were reviewed. Results The HCV status was recorded in 380 cases (67%). Of these, 193 had a test performed by their GP, 74 had been tested by another service and 113 had no evidence of being tested, but HCV status was recorded based on information provided by the patient himself. A total of 276 cases were identified as being HCV positive (prevalence 73%), with no difference in prevalence between the three sources of information (p=0.12). A history of injecting drug use was the major determinant of testing for HCV. Conclusions While a large proportion of drug users attending GPs for methadone maintenance treatment are known to be HCV positive, a considerable number have not been tested. Barriers to testing need to be explored to facilitate comprehensive screening.     

一叶萩碱全合成的研究

以1,4-环己二酮为原料经与哌啶缩合、还原、乙酸汞环合、碱催化分子内缩合等11步反应完成了一叶萩碱的全合成。合成品的熔点及光谱数据与天然一叶萩碱的熔点及光谱数据一致。     

Influenza and Respiratory Virus Surveillance,Vaccine Uptake,and Effectiveness at a Time of Cocirculating COVID-19: Protocol for the English Primary Care Sentinel System for 2020-2021

BackgroundThe Oxford–Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections.ObjectiveThe aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research.MethodsThe RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval.ResultsThe RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford–RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season.ConclusionsThe COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.     

Novel de novo mutation in sulfonylurea receptor 1 presenting as hyperinsulinism in infancy followed by overt diabetes in early adolescence

OBJECTIVE—Congenital hyperinsulinism, usually associated with severe neonatal hypoglycemia, may progress to diabetes, typically during the 4th decade of life in nonpancreatectomized patients. We aimed to genotype the ATP-sensitive K⁺ channel in a 10.5-year-old girl presenting with overt diabetes following hyperinsulinism in infancy.RESEARCH DESIGN AND METHODS—A female aged 10.5 years presented with new-onset, antibody-negative diabetes (A1C 10.6%). She was born large for gestational age (5 kg) to a nondiabetic mother and developed frequent hypoglycemic episodes, which persisted until age 3 years and responded initially to intravenous glucose and later to oral sweets. Currently, she is fully pubertal and obese (BMI 30.2 kg/m²), with a partially controlled convulsive disorder (since age 1 year) and poor school performance. Glucose levels were >11.1 mmol/l throughout 72 h of continuous glucose monitoring, with low insulin secretion during intravenous glucose tolerance testing. KCNJ11 and ABCC8 mutation analysis was performed, and the mutation identified was characterized in COSm6 cells.RESULTS—A novel, de novo heterozygous ABCC8 sulfonylurea receptor (SUR)1 mutation (R370S) was identified in the patient''s DNA but not in that of either parent. Cotransfection of Kir6.2 and mutant SUR1 demonstrate that the mutated protein is expressed efficiently at the cell surface but fails to respond to MgADP, resulting in minimal channel activity. Interestingly, the heterozygous channel (WT:R370S) responded well to glibenclamide, a finding that lead to the successful initiation of sulfonylurea therapy.CONCLUSIONS—This new ABCC8 mutation is associated with neonatal hyperinsulinism progressing within 10 years to insulinopenic diabetes. Consistent with in vitro findings, the patient responded to sulfonylurea treatment. The mechanism causing the relatively rapid loss in β-cell function is not clear, but it may involve mutation-induced increased β-cell apoptosis related to increased metabolic demand.Congenital hyperinsulinism (CHI) is a disorder of glucose metabolism characterized by dysregulated secretion of insulin resulting in hypoglycemia (1). Most cases are attributed to defects in pancreatic β-cell ATP-sensitive K⁺ (K_ATP) channels, which are critical for coupling glucose metabolism to membrane electrical activity and insulin release (2,3). K_ATP channels are activated (opened) by intracellular ADP and inhibited (closed) by ATP, the product of increased glucose metabolism. Closure of the K_ATP channel leads to membrane depolarization, which activates voltage-dependent Ca²⁺ channels, leading to an influx of Ca²⁺ and subsequently insulin granule exocytosis (3,4).Cloning and reconstitution studies demonstrate that the K_ATP channel is a hetero-octameric complex of two subunit types: the sulfonylurea receptor (SUR)1 and the inward rectifying K⁺ channel Kir6.2 (3,5,6). Given the key role of the K_ATP channel in insulin secretion, it is not surprising that inhibiting and activating mutations in the genes encoding the subunits of this channel can result in CHI (7,8) and neonatal diabetes (9,10), respectively. More interestingly, a dominantly inherited SUR1 mutation has been reported in a Finnish family, leading to CHI early in life and impaired insulin secretion or mild diabetes in adulthood (11,12).Here we report a novel, de novo heterozygous mutation in the SUR1 gene (ABCC8) (R370S) causing CHI in early infancy followed by overt diabetes presenting at age 10.5 years, suggesting that this mutation facilitates the development of early-onset nonautoimmune diabetes.